Oligodeoxynucleotide IMT504: Role on themicroglial cell activation and oligodendrocyteprogenitor cell proliferation and diff erentiation

PATRICIA MATHIEU; DÉBORA RODRÍGUEZ; ALEXIS SILVA SILVA; ANA ADAMO

Congreso; SAN2022 MEETING; 2022

Demyelination is a pathological process characterized by myelin loss from around axons, while remyelinationis the repair response through the restoration of myelin and the resolution of functional defi cits.Multiplesclerosis is a high-incidence infl ammatory demyelinating disease in which remyelination frequently fails.IMT504 (IMT) is a non-CpG oligodeoxynucleotide consisting of 24 nucleotides and characterized by 2 specifi cPyNTTTTGT sequences.Based on IMT immunomodulatory effects and regenerative properties, this work aimsto study its role in microglial activation and OL precursor (OPC) proliferation and differentiation. Primarycultures of OPCs and microglia were prepared from cerebral cortical tissue of 1- to 2-d-old rats. Microglia weretreated for 24 h with IMT for RNA extraction. qPCR analyses were carried out to evaluate microglial IL-1?, iNOS,Arg1 and TGF-? transcript expression. OPCs were treated with or without IMT, cultured for 2, 4 and 6 d andfi xed for immunocytochemical assays on PDGFR?+ OPCs, mature MBP+ OLs and Ki67+ proliferating cells.IMTproduced an abrupt change in cell morphology compatible with microglial activation and an increase in IL-1?and iNOS transcript levels. IMT also reduced the percentage of OPCs after 4 d and increased the percentage ofmature OLs after 4 and 6 d.These fi ndings unveil potentially benefi cial properties of IMT in neuroinfl ammationand oligodendrogenesis which may aid therapy development for demyelinating diseases.